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Technical Commentary TECHNICAL COMMENTARY Perospirone Introduction in symptoms and adverse effects - can vary Second generation antipsychotics (sometimes between individuals. referred to as ‘atypical’ antipsychotics) are a Method newer class of antipsychotic medication than first generation ‘typical’ antipsychotics. Second Owing to the vast number of reviews on generation antipsychotics are effective for the antipsychotics, we have included only positive symptoms of schizophrenia. It is information reported in the abstracts of 2 sometimes claimed that they are more effective Cochrane systematic reviews . This is because than first generation antipsychotics in treating the Cochrane internal review process ensures a the negative symptoms of schizophrenia, high level of scientific rigor and meta-analyses although the evidence for this is weak. Negative are usually conducted, giving treatment effect symptoms include a lack of ordinary mental sizes. Data from the abstracts were activities such as emotional expression, social supplemented from the full text when engagement, thinking and motivation, whereas clarification was required. When multiple copies positive symptoms include the experiences of of reviews were found and/or when findings perceptual abnormalities (hallucinations) and conflict, we present the most recent version and fixed, false, irrational beliefs (delusions)1. the most recent conclusions. Where no Second generation antipsychotics may also Cochrane review exists, other reviews with cause less extra-pyramidal side effects. These pooled data are included. include dyskinesias such as repetitive, Evidence was graded using the Grading of involuntary, and purposeless body or facial Recommendations Assessment, Development movements, Parkinsonism (cogwheel muscle and Evaluation (GRADE) Working Group rigidity, pill-rolling tremor and reduced or approach where high quality evidence such as slowed movements), akathisia (motor that gained from RCTs may be downgraded to restlessness, especially in the legs, and moderate or low if review and study quality is resembling agitation) and dystonias such as limited, if there is inconsistency in results, muscle contractions causing unusual twisting of indirect comparisons, imprecise or sparse data parts of the body, most often in the neck. These and high probability of reporting bias. It may effects are caused by the dopamine receptor also be downgraded if risks associated with the antagonist action of these drugs. One intervention or other matter under review are explanation for differences in producing these high. Conversely, low quality evidence such as side effects is that high potency first generation that gained from observational studies may be antipsychotics are usually selective dopamine upgraded if effect sizes are large, there is a receptor antagonists with a high affinity for the dose dependent response or if results are dopamine receptor and they induce reasonably consistent, precise and direct with extrapyramidal effects by the blockade of these low associated risks3. The resulting table dopamine receptors. In contrast, second represents an objective summary of the generation antipsychotics generally have a evidence, although the conclusions are solely lower affinity for the dopamine receptor and the opinion of staff of NeuRA (Neuroscience also block serotonin receptors, both of which Research Australia). mechanisms may play a role in mitigating the effects of dopamine blockade. Results This table summarises overall group We found one review that met our inclusion 4 effectiveness of perospirone, however criteria . individual treatment programs need to be tailored by trained clinicians as response - both NeuRA Perospirone August 2016 Margarete Ainsworth Building, Barker Street, Randwick NSW 2031. Phone: 02 9399 1000. Email: [email protected] Page 1 To donate, phone 1800 888 019 or visit www.neura.edu.au/donate/schizophrenia TECHNICAL COMMENTARY Perospirone Perospirone Compared to first generation antipsychotics Efficacy: Moderate to low quality evidence (small sample) suggests perospirone may be more effective than haloperidol for negative symptoms. Adverse effects: Moderate to high quality evidence (medium-sized sample, consistent, precise, direct) suggests perospirone may cause fewer extrapyramidal symptoms than aripiprazole, haloperidol, and risperidone (data combined). Compared to second generation antipsychotics Efficacy: Moderate quality evidence (medium to large samples, mostly inconsistent, precise, direct) suggests perospirone may be less effective for symptoms than other second generation antipsychotics. Adverse effects: Moderate to high quality evidence (medium-sized sample, consistent, precise, direct) suggests perospirone may cause fewer extrapyramidal symptoms than aripiprazole, haloperidol, and risperidone (data combined). Kishi T, Nakao I. Efficacy and tolerability of perospirone in schizophrenia: a systematic review and meta-analysis of randomized controlled trials. CNS Drugs 2013, 27(9):731–741 This review includes 2 double-blind and 3 open label RCTs (N = 562) that compared perospirone with olanzapine, quetiapine, risperidone, aripiprazole, haloperidol or mosapramine for 4-12 weeks. Compared to all antipsychotics combined, perospirone was inferior in the reduction of PANSS total scores (SMD 0.36, 95%CI 0.01 to 0.70, p = 0.04, I2 71%, p = 0.0006), and PANSS positive subscale scores (SMD 0.34, 95%CI 0.03 to 0.65, p = 0.03, I2 69%, p = 0.004). No differences were reported on PANSS negative, PANSS general subscale scores, discontinuation due to any cause, or inefficacy. Compared to second generation antipsychotics (olanzapine, quetiapine, risperidone, aripiprazole, or mosapramine), perospirone was inferior in the reduction of PANSS total scores (4 RCTs, N = 417, SMD 0.46, 95%CI 0.08 to 0.85, p = 0.02, I2 73%, p = 0.003), PANSS positive (SMD 0.42, 95%CI 0.03 to 0.80, p = 0.03, I2 72%, p = 0.003), PANSS negative (SMD 0.52, 95%CI 0.09 to 0.95, p = 0.02, I2 78%, p = 0.0004) and PANSS general subscale scores (SMD 0.37, 95%CI 0.04 to 0.70, p = 0.03, I2 62%, p = 0.02). Compared to haloperidol, perospirone was superior in reducing PANSS negative subscale scores (1 RCT, N = 145, SMD -0.41, 95%CI -0.74 to -0.05, p = 0.01), with no differences on any other PANSS scale. NeuRA Perospirone August 2016 Margarete Ainsworth Building, Barker Street, Randwick NSW 2031. Phone: 02 9399 1000. Email: [email protected] Page 2 To donate, phone 1800 888 019 or visit www.neura.edu.au/donate/schizophrenia TECHNICAL COMMENTARY Perospirone Risks Perospirone had lower scores relating to extrapyramidal symptoms than aripiprazole, haloperidol, and risperidone (3 RCTs, N = 292, SMD -0.30, 95%CI -0.53 to -0.07, p = 0.01, I2 0%, p = 0.43). No differences were reported for discontinuation due to side effects, akathisia, anxiety, at least one side effect, bradycardia, chest pain, constipation, depression, disturbance in gait, disturbance of speech, disturbance of swallowing, dizziness, dry mouth, dyskinesia, dystonia, dysuria, ejaculation disorder, epigastric distress, psychomotor excitement, fatigue, fever, headache, hyperprolactinemia, hypersalivation, hypertension, hypotension, increased appetite, insomnia, loss of appetite, mask-like face, nausea/vomiting, powerlessness, rigidity, skin problem, sleepiness, sedation, sweating, and tremor. Consistency in results‡ Inconsistent, apart from extrapyramidal symptoms. Precision in results§ Precise Directness of results║ Direct Explanation of acronyms CI = Confidence Interval, I² = the percentage of the variability in effect estimates that is due to heterogeneity rather than sampling error (chance), N = number of participants, p = statistical probability of obtaining that result (p < 0.05 generally regarded as significant), PANSS = Positive and Negative Syndrome Scale, SMD = standardised mean difference, RCT = randomized controlled trial NeuRA Perospirone August 2016 Margarete Ainsworth Building, Barker Street, Randwick NSW 2031. Phone: 02 9399 1000. Email: [email protected] Page 3 To donate, phone 1800 888 019 or visit www.neura.edu.au/donate/schizophrenia TECHNICAL COMMENTARY Perospirone Explanation of technical terms between variables. They are an indication of prediction, but do not confirm causality due to † Different effect measures are reported by possible and often unforseen confounding different reviews. variables. An r of 0.10 represents a weak association, 0.25 a medium association and Weighted mean difference scores refer to 0.40 and over represents a strong mean differences between treatment and association. Unstandardised (b) regression comparison groups after treatment (or coefficients indicate the average change in occasionally pre to post treatment) and in a the dependent variable associated with a 1 randomised trial there is an assumption that unit change in the independent variable, both groups are comparable on this measure statistically controlling for the other prior to treatment. Standardised mean independent variables. Standardised differences are divided by the pooled regression coefficients represent the change standard deviation (or the standard deviation being in units of standard deviations to allow of one group when groups are homogenous) comparison across different scales. which allows results from different scales to be combined and compared. Each study’s mean difference is then given a weighting depending on the size of the sample and the ‡ Inconsistency refers to differing estimates variability in the data. 0.2 represents a small
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